DNA replication proteins of E. coli and its phages have been purified and reactions catalyzed by them have been studied in vitro. In vivo, replication of lambda, a double-stranded DNA phage, requires many E. coli replication proteins, including the products of the dnaB, dnaG, dnaE, and dnaZ genes, and two lambda proteins, the products of the O and P genes. The lambda P protein has been purified and shown to form a physical complex with dnaB protein in vitro. Very likely, this interaction alters the specificity of dnaB protein in such a way that it can function in initiating lambda DNA replication. In vivo, replication of lambda-P22 hybrid phage containing the replication genes of P22 requires a combination of E. coli proteins and the products of P22 genes 12 and 18. The P22 12 protein has been purified and found to contain single-stranded DNA-dependent ATPase activity. In vitro, this protein functions in combination with dnaG protein to catalyze oligonucleotide synthesis with single-stranded DNA, including phi X174, fd, and G4 phage DNA and denatured lambda, P22, and calf thymus DNA. The interactions of E. coli proteins with phage proteins are being studied to learn about the molecular mechanisms by which DNA is replicated.